HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Alice C.L. Len, Shimona Starling, Maitreyi Shivkumar, Clare Jolly
HIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, we developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. We discovered HIV-1-induced activation of signaling networks during viral spread encompassing over 200 cellular proteins. Strikingly, pathways downstream of the T cell receptor were the most significantly activated, despite the absence of canonical antigen-dependent stimulation. The importance of this pathway was demonstrated by the depletion of proteins, and we show that HIV-1 Env-mediated cell-cell contact, the T cell receptor, and the Src kinase Lck were essential for signaling-dependent enhancement of viral dissemination. This study demonstrates that manipulation of signaling at immune cell contacts by HIV-1 is essential for promoting virus replication and defines a paradigm for antigen-independent T cell signaling.

Graphical abstract

Teaser

HIV-1 rapidly spreads between T cells. Len et al. have developed an approach to interrogate real-time signaling changes in infected and uninfected cells during viral dissemination. They report that HIV-1-induced cell-cell contact activates antigen-independent T cell signaling that is necessary for HIV-1 to spread efficiently between cells.


http://ift.tt/2ktXxRk